REEP2

receptor accessory protein 2, the group of Receptor accessory proteins

Basic information

Region (hg38): 5:138439056-138446969

Previous symbols: [ "C5orf19" ]

Links

ENSG00000132563 ∙ NCBI:51308 ∙ OMIM:609347 ∙ HGNC:17975 ∙ Uniprot:Q9BRK0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 72 (Moderate), mode of inheritance: Semidominant
• hereditary spastic paraplegia 72 (Supportive), mode of inheritance: AD
• hereditary spastic paraplegia 72 (Strong), mode of inheritance: AD
• hereditary spastic paraplegia 72 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 72A, autosomal dominant; Spastic paraplegia 72B, autosomal recessive	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	24388663

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the REEP2 gene.

• Hereditary spastic paraplegia 72 (84 variants)
• not provided (14 variants)
• Inborn genetic diseases (7 variants)
• not specified (1 variants)
• REEP2-related condition (1 variants)
• See cases (1 variants)
• Hereditary spastic paraplegia 5A (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the REEP2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				27	3	30
missense	1		28			29
nonsense		2				2
start loss			1			1
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			2	2		4
non coding			1	23	8	32
Total	1	3	32	50	11

Highest pathogenic variant AF is 0.00000657

Variants in REEP2

This is a list of pathogenic ClinVar variants found in the REEP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-138439208-C-T		REEP2-related disorder	Likely benign (Jun 27, 2019)
5-138439209-A-G		Hereditary spastic paraplegia 72	Uncertain significance (May 26, 2020)
5-138439214-G-C			Likely benign (Feb 01, 2019)
5-138439250-G-C		Hereditary spastic paraplegia 72	Likely benign (Jun 05, 2019)
5-138439254-C-T		Hereditary spastic paraplegia 72	Likely benign (Jun 23, 2022)
5-138439392-C-T			Benign (Mar 24, 2021)
5-138440751-G-A			Likely benign (Jun 21, 2021)
5-138440951-G-A			Likely benign (Apr 24, 2021)
5-138440999-C-T		Hereditary spastic paraplegia 72	Likely benign (Sep 10, 2023)
5-138441006-G-A		Hereditary spastic paraplegia 72	Benign (Oct 04, 2022)
5-138441006-G-C		Hereditary spastic paraplegia 72	Uncertain significance (Aug 26, 2022)
5-138441011-C-T		Hereditary spastic paraplegia 72	Likely benign (Mar 30, 2023)
5-138441061-C-T		Hereditary spastic paraplegia 72	Benign (Oct 11, 2023)
5-138441068-AC-A		Hereditary spastic paraplegia 72	Uncertain significance (Oct 17, 2021)
5-138441083-G-A		Hereditary spastic paraplegia 72	Uncertain significance (Sep 07, 2022)
5-138441091-G-T		Spastic paraplegia 72b, autosomal recessive	Pathogenic (Feb 06, 2014)
5-138441095-G-A		REEP2-related disorder	Likely benign (Jun 24, 2019)
5-138441096-G-A			Uncertain significance (-)
5-138441101-C-T		Hereditary spastic paraplegia 72	Likely benign (Oct 14, 2022)
5-138441104-T-C		Hereditary spastic paraplegia 72	Likely benign (Sep 19, 2022)
5-138441137-G-A			Likely benign (Apr 24, 2021)
5-138441242-C-T			Benign (Mar 24, 2021)
5-138441386-T-A		Hereditary spastic paraplegia 72	Pathogenic (Feb 06, 2014)
5-138441398-T-G		Hereditary spastic paraplegia 72	Pathogenic (Aug 23, 2022)
5-138441404-G-C		Hereditary spastic paraplegia 72	Uncertain significance (Jul 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
REEP2	protein_coding	protein_coding	ENST00000254901	8	7953

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.439	0.559	125736	0	5	125741	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.64	103	161	0.638	0.0000102	1629
Missense in Polyphen		18	50.896	0.35367		559
Synonymous	0.520	65	70.6	0.921	0.00000506	511
Loss of Function	2.74	3	14.1	0.212	7.72e-7	156

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for endoplasmic reticulum (ER) network formation, shaping and remodeling. May enhance the cell surface expression of odorant receptors (By similarity). {ECO:0000250, ECO:0000269|PubMed:24388663}.
• Pathway: Signaling by GPCR;Signal Transduction;Olfactory Signaling Pathway;G alpha (s) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.129
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.12

Haploinsufficiency Scores

• pHI: 0.351
• hipred: Y
• hipred_score: 0.731
• ghis: 0.629

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Reep2

Gene ontology

• Biological process: regulation of intracellular transport;protein transport into membrane raft;sensory perception of bitter taste;sensory perception of sweet taste;endoplasmic reticulum tubular network organization
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;cytoplasmic microtubule;integral component of plasma membrane
• Molecular function: taste receptor binding